CN109641123A

CN109641123A - Method and apparatus for adrenal nerve modulation

Info

Publication number: CN109641123A
Application number: CN201780052106.8A
Authority: CN
Inventors: 琳内·E·斯旺森; 威廉·C·斯托弗瑞根; 布莱恩·A·克拉克; 迈克尔·X·戈韦亚; 丹尼斯·B·维尔纳; 纳塔利·A·布里尔; 普拉莫德辛格·H·塔库尔
Original assignee: Boston Scientific Neuromodulation Corp
Current assignee: Boston Scientific Neuromodulation Corp
Priority date: 2016-08-23
Filing date: 2017-08-22
Publication date: 2019-04-16
Anticipated expiration: 2037-08-22
Also published as: US10441788B2; JP2019524373A; EP3503961B1; EP3503961A1; AU2017316673A1; CN109641123B; US20180056062A1; WO2018039285A1

Abstract

All aspects of this disclosure are directed to for that will treat the adrenal devices, systems, and methods for being delivered to patient.Described device, system and method can include: lead main body is attached to adrenal a part of patient；And multiple electrodes, it is arranged along lead main body.In addition, one or more of multiple electrodes can deliver stimulation energy to adjust from the catecholamine of the chromaffin cell in adrenal gland and discharge.

Description

Method and apparatus for adrenal nerve modulation

Cross reference to related applications

This application claims the priority for the Provisional Application No. 62/378,419 that August in 2016 is submitted on the 23rd, the provisional applications It is incorporated herein by reference in their entirety.

Technical field

This disclosure relates to for providing the Medical Devices and method of stimulation therapy.More specifically, this disclosure relates to for inciting somebody to action Treatment is delivered to the adrenal device and method of patient.

Background technique

Electro photoluminescence can treat in a variety of diseases and illness.Lead for electro photoluminescence can be implanted into target area, Adjacent objects region or in close-proximity target zone.In some cases, one or more leads can be arranged in nerve, muscle or Other adjacent tissues.

Dysfunction or catecholamine (such as norepinephrine, adrenaline and the DOPA of adrenal medella system Amine) abnormal level with include that depression, fibromyalgia, confirmed fatigue, chronic ache, migraine, orthostatic do not tolerate, uprightly Property tachycardia syndrome (Postural Orthostatic Tachycardia Syndrome (POTS)) and other diseases shape The symptom of state is associated.Adrenal stimulation can directly discharge or catecholamine is prevented to be discharged into blood flow.

Sympathetic nerve aixs cylinder terminates at the chromaffin cell in adrenal medella before the neuromere of nervus visceralis.Two thermophilic chromium Cell mass, a release adrenaline and a release norepinephrine, show different innervation modes.Knot Fruit can be used different stimulus modalities and these levels be changed independently to push the abnormal level of catecholamine to normal water It is flat, to for one of various morbid states associated there or a variety of provide treatment and/or diagnosis and treatment.

Summary of the invention

In example 1, a kind of device for the delivering treatment of the adrenal gland of patient, which includes: lead main body, It is configured to attach to adrenal a part of patient and engages adrenal capsule；And multiple electrodes, along lead Main body arrangement, at least one of multiple electrode are configured as delivering stimulation energy to adjust from the chromaffin cell in adrenal gland Catecholamine release.

In example 2, the device of example 1, wherein lead main body is configured to attach to capsule week connective tissue (pericapsular connective tissue) or adrenal capsule.

In example 3, device described in any one of example 1 or 2, wherein the lead main body be configured as being attached to It is at least one of lower: capsule week connective tissue, the outer surface of adrenal capsule, adrenal capsule inner surface and adrenal gland Capsule the inner surface and the outer surface between.

In example 4, the device of any of example 1-3, wherein lead main body is configured as through lead main body and suffers from Person capsule week connective tissue or adrenal a part mechanical attachment and adhesive attachment at least one of and be attached to trouble Adrenal a part of person.

In example 5, the device of example 4, wherein lead main body further includes barb, sutural lamina (suture tab), spiral At least one of part and pawl, with adrenal a part for lead main body to be mechanically attached to patient.

In example 6, the device of example 4 further includes at least one of tissue glue, adhesive and hydrogel, for inciting somebody to action Lead main body is attached to adrenal a part of patient.

In example 7, the device of any of example 1-6, wherein at least one of the multiple electrode includes piercing through Partially and it is configured as being pierced into adrenal gland.

In example 8, the device of example 7, wherein be configured at least one of multiple electrodes being pierced into adrenal gland also Delivering stimulation energy is configured to discharge to adjust from the catecholamine of the chromaffin cell in adrenal gland.

In example 9, the device of any one of example 1-8 further includes biosensor, is configured as in measurement or less At least one: the heart rate of patient, the heart rate variability of patient, the respiratory rate of patient, the activity level of patient, patient catechu Phenol amine level, the catecholamine metabolism object of patient, the normetanephrine of patient are horizontal, patient metanephrine is horizontal, The cortisol metanephrine levels of creatinine levels, patient in Urine in Patients, the posture of patient, the temperature of body patient, The cardiac output of patient, the angiosthenia of patient, the sleep state of patient and the Depth of sleep of patient.

In example 10, the device of example 9, wherein the measurement result in response to biosensor and the input from patient At least one of change stimulation energy.

In example 11, the device of example 9 further includes controller, which is configured as communicating with biosensor And in response to the delivering of communication instruction stimulation energy.

In example 12, the device of any of example 1-11 further includes controller, and it is logical which is configured as instruction At least one electrode delivering stimulation energy in multiple electrodes is crossed, is released with adjusting the catecholamine of the chromaffin cell in adrenal gland It puts.

In example 13, the device of example 12, wherein controller is configured as intermittently or continuously indicating by multiple The Different electrodes set of electrode delivers stimulation energy.

In example 14, the device of example 12, wherein controller is configured as indicating the metabolism time based on catecholamine Stimulation energy is delivered by least one electrode in multiple electrodes on the duty cycle.

In example 15, the device of example 12, wherein controller is configured as indicating the frequency between 2Hz and 20kHz Stimulation energy is delivered by least one electrode in multiple electrodes.

In example 16, a kind of device for the delivering treatment of the adrenal gland of patient, which includes: lead main body, It includes at least one attachment mechanism, which is configured to attach to adrenal a part of patient, lead master Body is configured as engaging adrenal capsule；And multiple electrodes, it is arranged along lead main body, multiple electrode configuration is to pass through At least one of multiple electrodes deliver stimulation energy, are discharged with adjusting from the catecholamine of the chromaffin cell in adrenal gland.

In example 17, the device of example 16, on paddle component, which is arranged in plurality of electrode arrangement The distal end of lead main body.

In example 18, the device of example 17, wherein paddle component is configured as, in response to the portion from deployment system It affixes one's name to and expands to deployment configuration, and close up and fold into delivering configuration in response to the retraction in deployment system.

In example 19, the device of example 17, wherein paddle component is flexible and is configured to connect in delivering configuration Merge the adrenal gland week connective tissue or adrenal a part for being attached to patient.

In example 20, the device of example 16 includes further or alternatively at least one thermoelectric element, is configured to Cooling adrenal gland is discharged with adjusting from the catecholamine of the chromaffin cell in adrenal gland.

In example 21, the device of example 16, on paddle component, which is arranged in plurality of electrode arrangement The distal end of lead main body, and at least one thermoelectric element is arranged together with paddle component.

In example 22, the device of example 16, wherein lead main body is configured as being attached at least one of the following: kidney Upper gland week connective tissue, the outer surface of adrenal capsule, the inner surface of adrenal capsule and adrenal capsule inner surface and Between outer surface.

In example 23, the device of example 16, wherein lead main body is configured as, and is attached by mechanical attachment and adhesive At least one of and be attached to the adrenal gland week connective tissue or adrenal a part of patient.

In example 24, the device of example 23, wherein lead main body further include the barb for mechanical attachment, sutural lamina, At least one of helical member and pawl.

In example 25, the device of example 23, further or alternatively include tissue glue, adhesive and hydrogel in extremely Few one kind, with adrenal a part for lead main body adhesive to be attached to patient.

In example 26, the device of example 16, at least one of plurality of electrode is configured as being pierced into adrenal gland Lead main body to be attached to adrenal a part of patient.

In example 27, a kind of system for the delivering treatment of the adrenal gland of patient, which includes: lead main body, It is configured as engaging adrenal capsule；Multiple electrodes arrange, the multiple electrode is configured as passing through along lead main body At least one of the multiple electrode delivers stimulation energy, is released with adjusting from the catecholamine of the chromaffin cell in adrenal gland It puts；Biosensor is configured as at least one physiological reaction of measurement patient；And controller, it is operatively coupled to To lead and biosensor, the controller be configured that instruction by least one of multiple electrodes deliver stimulation energy, from Biosensor receives the signal of the data of at least one physiological reaction with instruction patient, analysis signal to calculate stimulation energy The variation of amount and it is signal-based analysis and wire communication to change stimulation energy.

In example 28, the system of example 27, wherein biosensor is configured as measurement at least one of the following: The heart rate of patient, the respiratory rate of patient, the activity level of patient, the catecholamine levels of patient, is suffered from the heart rate variability of patient Catecholamine metabolism object, the normetanephrine of patient of person is horizontal, patient metanephrine is horizontal, in Urine in Patients Creatinine levels, the cortisol metanephrine level of patient, the posture of patient, the body temperature of patient, the cardiac output of patient, trouble The Depth of sleep of the angiosthenia of person, the sleep state of patient and patient.

In example 29, the system of example 27, wherein controller is additionally configured to intermittently or continuously indicate by more The Different electrodes set of a electrode delivers stimulation energy.

In example 30, the system of example 27, wherein when controller is additionally configured to indicate the metabolism based on catecholamine Between stimulation energy is delivered by least one electrode in multiple electrodes on the duty cycle.

In example 31, the system of example 27, wherein controller is additionally configured to indicate the frequency between 2Hz and 20kHz Rate delivers stimulation energy by least one electrode in multiple electrodes.

In example 32, a method of it delivers and treats to the adrenal gland of patient, this method comprises: lead main body is delivered To the adrenal gland of patient；A part of lead main body is attached in the adrenal capsule or capsule week connective tissue of patient；And Stimulation energy is delivered by least one of multiple electrodes for arranging along lead main body, to adjust from thermophilic in adrenal gland The catecholamine of chromium cell discharges.

In example 33, the method for example 32, wherein it includes that lead main body is attached that the part of lead main body, which is attached to capsule, Be connected at least one of the following: capsule week connective tissue, the outer surface of adrenal capsule, adrenal capsule inner surface and Between the inner surface and the outer surface of adrenal capsule.

In example 34, the method for example 32, wherein it includes passing through mechanical attachment that the part of lead main body, which is attached to capsule, With at least one of adhesive attachment and be attached a part of lead main body.

In example 35, the method for example 34, wherein a part of mechanical attachment lead main body further includes using lead master Lead main body is attached to capsule by barb, sutural lamina, helical member and the pawl that a part of body is arranged together.

Although disclosing multiple embodiments, the other embodiments of the disclosure to those skilled in the art will be from Described in detail below to become apparent, which has shown and described the illustrative embodiments of the disclosure.Therefore, attached drawing It is in itself considered illustrative and not restrictive with detailed description.

Detailed description of the invention

Fig. 1 is the example diagram of adrenal gland treatment system according to an embodiment of the present disclosure.

Fig. 2 is the plan view of adrenal gland treatment system according to an embodiment of the present disclosure.

Fig. 3 A is the example diagram of adrenal gland treatment lead-line configuration according to an embodiment of the present disclosure.

Fig. 3 B is the example diagram of another adrenal gland treatment lead-line configuration according to an embodiment of the present disclosure.

Fig. 3 C is the example diagram of another adrenal gland treatment lead-line configuration according to an embodiment of the present disclosure.

Fig. 4 A is the example diagram of adrenal gland treatment lead and deployment system according to an embodiment of the present disclosure.

Fig. 4 B is adrenal gland treatment lead shown in Fig. 4 B according to an embodiment of the present disclosure disposed from deployment system Example diagram.

Fig. 4 C is the treatment of adrenal gland shown in Fig. 4 A- Fig. 4 B according to an embodiment of the present disclosure being deployed on adrenal gland The example of lead illustrates.

Fig. 4 D is that adrenal gland shown in Fig. 4 A- Fig. 4 C according to an embodiment of the present disclosure including tether (tether) is controlled Treat the example diagram of lead.

Fig. 5 is the example diagram of adrenal gland treatment lead according to an embodiment of the present disclosure.

Fig. 6 is the example diagram of adrenal gland treatment system according to an embodiment of the present disclosure.

Fig. 7 A is the example diagram of another adrenal gland treatment system according to an embodiment of the present disclosure.

Fig. 7 B is according to an embodiment of the present disclosure include in the adrenal gland treatment system shown in Fig. 7 A thermoelectricity member The example of part illustrates.

Although the disclosure may be modified such that various modifications and alternative form, specific embodiment shows by example in the accompanying drawings Out, it and is discussed in more detail below.It is intended, however, that not being that the disclosure is limited to described specific embodiment.On the contrary, this public affairs It opens and is intended to cover all modifications, equivalents, and substitutions object fallen within the scope of the disclosure being defined by the following claims.

It, can be mutual since the range (such as those disclosed immediately above) of term used herein and measurement result is related It uses with changing " about " and " approximation " refers to the measurement result including the measurement result, and further include and the measurement result Fairly close any measurement result, but may differ by fairly small amount, such as those of ordinary skill in the related art will manage Solution and be easy it is determining, due to measuring result error, the difference of measurement result and/or manufacturing equipment calibration, reading and/or setting Set the mistake in measurement result, the difference in view of measurement result associated with other assemblies, specific embodiment and/or The adjustment of people or machine to progress such as the inaccurate adjustment and/or manipulation of object, to optimize performance and/or structural parameters.

Although term " block " may be used herein to indicate the different elements illustratively used, which should not be by Be construed as to imply that in various pieces disclosed herein or between any requirement or particular order.Similarly, although illustrative side Method can be indicated by one or more attached drawings (for example, flow chart, communication process etc.), but attached drawing is not necessarily to be construed as implying this In various steps disclosed in text or between any requirement or particular order.However, some embodiments may need certain steps Certain sequences between rapid and/or certain steps such as can be expressly recited herein and/or can such as understand from the property of step itself (for example, the execution of certain steps may depend on the result of previous step).In addition, " set " of entry, " subset " or " group " (example Such as, input, algorithm, data value etc.) it may include one or more entries, and similarly, the subset or subgroup of entry can be with Including one or more entries." multiple " mean more than one.

Specific embodiment

Various aspects of the disclosure is related to the device, method and system side for the adrenal Neuroendocrine regulation of patient Method.The depolarising or nervus visceralis effect of the chromaffin cell film in adrenal medella are stimulated, chronic fatigue syndrome and fibre are used for The pain of dimension myalgia and non-pain symptom and the other diseases state with neurotransmitter or neurohormone dysfunction.On kidney Chromaffin cell synthesis, storage and catecholamine secretion (for example, norepinephrine, adrenaline) in gland medullary substance.Adrenal gland Stimulation can lead to the active increase of several catecholamine biosynthetic enzymes or generate blocking effect, and cause catecholamine biological Synthesis rate or chromaffin cell exocytosis or chromaffin cell sensibility increase or decrease, and so as to cause catecholamine and come from thermophilic chromium The secretion or blocking of other chromaffin particles ingredients of cell.

Fig. 1 is the example diagram of adrenal gland treatment system 100 comprising is drawn according to the treatment of the adrenal gland of the embodiment of the present disclosure Line 102 and controller 104.Lead 102 may include elongated cylindrical lead main body 106.Lead 102 includes being disposed in lead Multiple electrodes 108 in main body 106.Electrode 108 can be around lead 102 circumferentially, as what is installed around lead main body 106 Annular electrode.In embodiment, electrode 108 can at least approximately extend around the circumference of lead main body 106.In embodiment In, one or more electrodes 108 can extend partially around the circumference of lead main body 106.In some cases, for example, it is more A electrode 108 can be the segmented electrode around 106 circumferential and axial of lead main body arrangement.In multiple electrodes 108 shown Each label is, but the actual quantity and shape of lead and electrode vary depending on the application.

As shown, adrenal gland treatment lead 102 is operably coupled to controller 104.It is disposed with the company of controller 104 It connects device 110 and one end of adrenal gland treatment lead 102 is couple to controller 104, thus operationally (for example, communicatedly, electrically Ground and/or physically) electrode 108 is couple to the internal electronic device in controller 104.In embodiment, controller 104 can To be configured as wirelessly communicating with one or more leads 102, in this case, controller 104 may include one or more A radio antenna and/or coil etc..Controller 104 can also include shell 112, and shell 112 includes and accommodates electronics device Part and other assemblies.In embodiment, controller 104 may include the impulse generator of implantable patient's body (for example, can plant Enter impulse generator (IPG)), or be configurable to be positioned at patient external.In the case where controller 104 is implantable, Shell 112 can be formed by conduction, biocompatible material (such as titanium), and can form hermetically sealed compartment, The middle influence for protecting internal electronic device from bodily tissue and fluid.

Shell 112 can surround sensing circuit 114, and sensing circuit 114 is configured as receiving from one or more electrodes 108 The physiological signal obtained by the one or more electrode 108.Shell 112 can also surround pulse generation circuit 116, and pulse generates Circuit 116 delivers stimulation energy via one or more electrodes 108.According to various embodiments, sensing circuit 114 (or its aspect) And/or pulse generation circuit 116 (or its aspect) can be configured as and be implanted into the patient and/or arrange outside the patient's body.? That is for example, in embodiment, sensing circuit 114 and pulse generation circuit 116 can integrate and be disposed in implantable doctor It treats in the processor in equipment (for example, controller 104) and/or external medical equipment.Sensing circuit 114 (or its aspect) and/ Or pulse generation circuit 116 (or its aspect) can be implemented with any combination of hardware, firmware and software.For example, sensing electricity Road 114 can be or include the first algorithm, virtual processor and/or the process implemented by processor, and similarly, pulse is raw Can be at 116 circuit of circuit or include by processor implement the second algorithm, virtual processor and/or process.In embodiment In, sensing circuit 114 can be or the first set including physics and/or virtual circuit element, and similarly, and pulse generates Circuit 116 can be or the second set including physics and/or virtual circuit element.

In embodiment, controller 104 may include programmable microcontroller or microprocessor, and may include one Or multiple programmable logic device (PLD) or specific integrated circuit (ASIC).In some embodiments, controller 104 can also To include memory.Although describing the implementation of this system 100 in conjunction with the controller 104 with the framework based on microprocessor Example, but it is to be understood that if desired, controller 104 (or other equipment) can be in the integrated circuit frame of any logic-based Implement in structure.Controller 104 may include digital-to-analogue (D/A) converter, modulus (A/D) converter, timer, counter, filtering Device and/or switch etc..

Sensing circuit 114 can be configured as the physiological signal for receiving and being obtained by one or more electrodes 108, and analyzes and connect The physiological signal received is to identify treatment region.According to embodiment, physiological signal may include intrinsic electrical activity and/or to application Stimulus signal physiological reaction etc..For example, sensing circuit 114 can be configured as acquisition physiological signal, which is Reaction to the stimulus signal for using one or more electrodes 108 to give, and the signal is analyzed to identify treatment position.In reality It applies in example, sensing circuit 114 can be configured as movement, adrenal electrical activity and/or other physiological signals of assessment patient To identify treatment region.

In embodiment, treatment region can be the region including adrenal a part, and being identified as may be with kidney Upper gland shape condition is associated.For example, for treat such as chronic fatigue syndrome, fibromyalgia, orthostatic do not tolerate, intestines easily swash Syndrome (IBS), Crohn disease, emotional handicap/depression or other diseases with neurotransmitter or neurohormone dysfunction In the embodiment of the illness of diseased state, adrenal gland treatment lead 102 can be inserted in associated with illness by clinician The areas adjacent of one or two of the adrenal gland of patient or on, operate controller 104 (for example, if controller 104 exists It is external then be manually operated, and via telemetry operations if controller 104 is implanted into), make controller 104 via one or Stimulation energy is delivered to the region selected by multiple electrodes 108.It is anti-by assessing the electricity obtained by one or more electrodes 108 It answers, controller 104 and/or clinician can determine whether the region selected is treatment region (for example, if life to stimulation Reason reaction instruction therapeutic effect, then the region selected can be identified as treatment region).In embodiment, by determining one Or multiple adrenal regions (giving at least some improvement that stimulation energy leads to symptom for the region), clinician can be with Identify treatment region.

Stimulation energy can be according to the pulsed electrical waveform of one or more electrodes 108 of the set of stimulation parameter Form may be programmed into controller 104 and/or be sent to controller 104 etc..Stimulation parameter may include, such as The electrode sets of electrode are defined, the electrode is activated as anode (just), cathode (negative), unlatching, closes (zero)；It distributes to each The percentage (electrode configuration of subdivision) of the stimulation energy of electrode；And/or electric pulse parameter, impulse amplitude is defined (with milliampere Or volt is unit measurement, depends on whether controller 104 to one or more electrodes 108 supplies constant current or constant electricity Pressure), pulse duration (being measured as unit of microsecond), pulse rate (being measured with pulses per second), impulse waveform and/or prominent Hair rate (is measured as stimulation opening time duration X and duration Y is closed in stimulation).Pulse generation circuit 116 can lead to It crosses multiple channels or stimulation energy is only delivered to by one or more electrodes 108 by single channel.Stimulation energy can be used for knowing Other treatment region and/or stimulation therapy is provided to the treatment region that identifies or changes over time treatment region to prevent at one Position fatigue.

Stimulation energy can be sent to tissue in a manner of monopole (or single pole) or multipole (for example, bipolar, three extremely etc.).When Unipolar stimulation occurs when the one or more electrodes 108 selected are activated and sends tissue for stimulation energy.When two electrodes 108 when being activated as anode and cathode, occurs bipolar stimulation (a type of multipole stimulation), so that between the electrode of activation Send stimulation energy.When the electrode 108 of more than two (for example, three, four etc.) is activated, such as two are used as anode simultaneously And third is used as cathode as cathode or two and third is used as anode, and multipole stimulation can also occur.In certain feelings Under condition, pulse generation circuit 116 can flow through the size of the electric current of each electrode with independent control.In these cases, electric current is sent out Raw device can be used for supplying the amplitude of current regulation, generate independent current source with selectively one or more electrodes 108.

Fig. 2 is the plan view of adrenal gland treatment system 200 according to an embodiment of the present disclosure.Adrenal gland treatment system 200 It may include at least one implantable adrenal gland stimulation lead 202,204, impulse generator (PG) 206, external remote (RC) 208, the programmable device (CP) 210 and external charger 214 of clinician.In some cases, PG 206 can operationally coupling (and in embodiment, physical couplings) are connect to adrenal gland stimulation one or two of lead 202,204, can carry with The multiple electrodes 216 of array arrangement.PG 206 may include pulse generation circuit, and the pulse generation circuit is according to stimulation parameter Set will be by the electro photoluminescence energy delivery in the form of pulsed electrical waveform (that is, time series of electric pulse) to multiple electrodes 216. PG206 can be implantable PG (and IPG), outside PG or can indicate include one or more implantable devices and/or The system of one or more external equipments being operatively coupled to.

In some cases, RC 208 can be used for controlling PG 206 via 226 telemetering of communication link.RC 208 can also be modified Stimulation parameter by programming is with active control by the characteristic of the electro photoluminescence energy exported of PG 206.RC208 can be via communication chain Road 228 is communicated by RC 208 with PG 206 to execute these functions indirectly.CP 210 can be used to change and join to stimulation Several or stimulus quality change.CP 210 can be communicated directly with PG206 and be led to via communication link (not shown) and PG 206 Letter.External charger 214 can be the portable device for charging via charging link 230 to PG 206, the charging link 230 can be such as induction charging link, radio frequency (RF) charging link, illumination, ultrasonic wave and/or magnetism.

In embodiment, communication link 226,228 and 230 can be or including wireless communication link, such as short distance Radio link, bluetooth, IEEE 802.11 and/or proprietary wireless protocols etc..In embodiment, for example, communication link 226, one or more of 228 and 230 Bluetooth Low Energy radio (bluetooth 4.1) or similar agreement be can use, and can To utilize 2.40 to the working frequency within the scope of 2.48GHz.Term " communication link " can refer to exist between at least two devices At least one side is passed up the ability of certain type of information, and should not be construed as limited to it is direct, lasting or Otherwise limited communication channel.That is, communication link can be persistent communication link, interval according to embodiment Communication link and/or ad-hoc communication link etc..Communication link can refer to the direct communication between one or more equipment, and/ Or it goes between one or more equipment via at least one other equipment (for example, transponder, router and/or hub etc.) Into indirect communication.Communication link can promote the unidirectional and/or two-way communication between chained device.

Any amount of various communication means and agreement can be used via communication link, to promote adrenal gland treatment system The communication between equipment in 200.It is, for example, possible to use wired and or wireless communications methods.Wire communication method can wrap Include, such as, but not limited to, the communication of the traditional copper wire of such as DSL, such as ISDN and cable modem broadband technology and Optical fiber, and wirelessly communicate may include cellular communication, satellite communication, radio frequency (RF) communication, infrared communication, induction, conduction and/or Acoustic communication etc..

Fig. 1 and Illustrative components shown in Figure 2 are not intended to use scope or function to the embodiment of published subject It is proposed any restrictions.Illustrative components also should not be interpreted as having with there is shown with any single component or component combined Any dependence or requirement closed.In addition, in embodiment, describe in any one of Fig. 1-Fig. 2 any one or it is more A component can be integrated with the various other components (and/or unshowned component) wherein described, and all these components are all recognized To be in the range of disclosed theme.For example, can be used for reference to Fig. 1, Fig. 3 or Fig. 4 adrenal gland stimulation lead described Adrenal gland treatment system 200.In addition, adrenal gland treatment system 200 can form a part with reference to Fig. 6 system described.

Fig. 3 A- figure C is the exemplary diagram according to an embodiment of the present disclosure with different configuration of adrenal gland treatment lead 300 Show.Adrenal gland treatment lead 300, which can be individually used for delivering to the adrenal gland of patient, treats, or as the kidney to patient A part of device, method or system that upper gland delivering is treated.Adrenal gland treatment lead 300 may include lead main body 302 and with Its multiple electrodes 304,306,308 arranged together.Adrenal gland treatment lead 300 can be connect (for example, as referred to controller Fig. 1 and Fig. 2 shows with description), with to arranged along lead main body 302 multiple electrodes 304,306,308 supply stimulation ginseng Number.Lead main body 302 can be configured as the adrenal a part for being attached to patient and engage adrenal capsule.Lead master Body 302 can be configured as the adrenal a part for being attached to patient and engage fascia renalis, Gerota fascia, kidney week rouge Fat, perirenal space, anterior pararenal space, capsule or cortex.In addition more and as being described in further detail see, for example Fig. 5-Fig. 6 At least one of a electrode 304,306,308 is configured as delivering stimulation energy to adjust from the chromaffin cell in adrenal gland Catecholamine release.It can also include: button 310 that adrenal gland, which treats lead 300, be configured to promote for lead to be attached on kidney Gland and its stimulation；And Screw Anchor 312.In addition, one or more of multiple electrodes 304,306,308 can be configured to sensing by In delivering stimulation energy and the catecholamine that discharges.Button 310 can be by the material with characteristic identical as lead main body 302 It is formed.In some cases, button 310 can be formed and is sized and shaped as, by being arranged in multiple electrodes 304,306,308 Thereon, stimulation surface area bigger compared with lead main body 302 is provided.

Button 310 can have the flexibility bigger than lead main body 302, and be configurable to meet adrenal gland so as to attached It is connected to thereon.More specifically, button 310 can take adrenal shape when being attached to adrenal gland.In addition, button 310 can To have the width of the width less than lead main body 302.In some cases, button 310 can be attached to adrenal one A part of partial adrenal gland treatment lead 300.Adrenal gland is surrounded by adipose capsule.Button 310 can be attached to the appearance of capsule Face, intracapsular, capsule inner surface (for example, between capsule and adrenal gland) or it is directly attached to adrenal gland.Therefore, the width of button 310 Degree may be approximately equal to or be less than adrenal capsule.

Screw Anchor 312 can be configured as direct or indirect (via capsule) and lead main body 302 be anchored to adrenal gland.At certain In a little situations, Screw Anchor 312 can be configured as the electrode other than electrode 304,306,308.The length of Screw Anchor 312 can To depend on anchor station (for example, compared with being anchored to capsule or adrenal gland substantially, the longer length when being anchored to adrenal gland). Screw Anchor 312, which can be configured as, mitigates the migration of lead main body 302 in implantation, and ensures the positive fixation on adrenal gland.

In addition, button 310 can be arranged along any part of lead main body 302.As shown in Fig. 3 A, 310 edge of button Lead main body 302 middle section arrangement.Lead main body 302 include multiple electrodes 304 on the side of button 310, 306, some in 308, and other electrodes in the multiple electrodes 304,306,308 on the other side of button 310.At certain In a little situations, after button 310 is implanted into and/or is fixed to adrenal gland, the position of adjustable button 310.Button 310 can be with Lead main body 302 is frictionally engaged, so that the coupling of button 310 Yu lead main body 302 will be overcome by the power that doctor applies.Button 310 can also be attached or coupled to lead main body 302 by adhesive of medical.Doctor can be before being implanted into lead main body 302 Or the positioning of button 310 is adjusted after button 310 is fixed to adrenal gland.As a result, doctor can be by by button 310 Implantation and/or fixed to adjusting multiple electrodes along the length movable button 310 of lead main body 302 before or after adrenal gland 304,306,308 relative to adrenal positioning.As shown in Fig. 3 B, button 310 can couple or be attached to lead main body 302 distal end.In some cases, the distal end of lead main body 302 may include multiple buttons 310.

As shown in Fig. 3 C, multiple electrodes 304,306,308 can be arranged around the periphery of button 310.In certain feelings Under condition, different from the length of across lead main body 302, being arranged in such a way multiple electrodes 304,306,308 can promote pierce Sharp energy is directed to smaller target area.

Fig. 4 A is the example diagram of adrenal gland treatment lead 400 and deployment system 402 according to an embodiment of the present disclosure.Such as Shown in Fig. 4 A, adrenal gland treatment lead 400 is arranged in deployment system 402.Adrenal gland treatment lead 400 can be individually used for Treatment is delivered to the adrenal gland of patient or as one for that will treat the adrenal device for being delivered to patient, method or system Part.It may include paddle component 404 that adrenal gland, which treats lead 400,.Deployment system 402 can have cylindrical shape, remote at it There is circular open at end.Adrenal gland treatment lead 400 including lead main body 406 can be loaded into delivering system in place at either end In system 402.When loading adrenal gland treatment lead 400 wherein, paddle component 404 can be in 402 interior folding of deployment system (collapse).As shown in Fig. 4 A, paddle component 404 can be rolled on itself in 402 interior folding of deployment system.? In some cases, paddle component 404 can close up in deployment system 402, wrinkle, fold or bending are to fold.In certain feelings Under condition, deployment system 402 can be delivery catheter.

Fig. 4 B is that adrenal gland treatment shown in Fig. 4 B according to an embodiment of the present disclosure disposed from deployment system 402 is drawn The example of line 400 illustrates.Fig. 4 B, which is shown, treats lead 400 in deployment/delivering configuration adrenal gland, and Fig. 4 A shows place Lead 400 is treated in the adrenal gland of delivering configuration.Paddle component 404 can be configured as, in response to from deployment system 402 It disposes and expands to deployment configuration (shown in Fig. 4 B), and close up and fold in response to the retraction in deployment system 402 (shown in Fig. 4 A) is configured to delivering.

In addition and as shown in Figure 4, paddle component 404 may include multiple electrodes 408.Multiple electrodes 408 are arranged in On paddle component 404, the far-end of lead main body 406 can be arranged in.Multiple electrodes 408 are configurable to deliver by it Stimulation energy is discharged with adjusting from the catecholamine of the chromaffin cell in the adrenal gland of patient.Adrenal gland treats lead 400 can be with Connect with controller (for example, as with reference to Fig. 1 and Fig. 2 shows with described in), with multiple to being arranged together with paddle component 404 Electrode 408 supplies stimulation parameter.In addition, one or more of multiple electrodes 408 can be configured to sense the stimulation delivered The biomarker of energy affect.The sensing level of the catecholamine discharged can be used as feedback and be supplied to controller, can Desired catecholamine emission levels are realized to change stimulation energy.In some cases, paddle component 404 may include and its The thermoelectric element 410 arranged together.Thermoelectric element 410 can provide cooling effect for adrenal gland.Such as B is schemed into one with reference to Fig. 7 A- Step detailed description, cooling adrenal thermoelectric element 410 can also adjust the catecholamine from the chromaffin cell in adrenal gland Release.More specifically, thermoelectric element 410 (for example, Peltier (Peltier) element) is configurable to cool down adrenal periphery Region.Thermoelectric element 410, which is applied to medullary substance (wherein, on it or near), can produce catecholamine in regulating blood flow The result of cyclical level.In some cases, thermoelectric element 410 can be supplied at adrenal artery, close to or within Intravascular space in apply cooling effect.Thermoelectric element 410 can be supplied within the temperature range of 4 degrees Celsius to 32 degrees Celsius It is cooling.

In some cases, lead main body 406 or part of it are configurable to adrenal one that is attached to patient Point.More specifically, paddle component 404 or lead main body 406 are configurable to the capsule of one of engagement adrenal gland.As above mentioned , paddle component 404 can be flexible and be configured to engage and be attached to the adrenal portion of patient in delivering configuration Divide (for example, capsule).Paddle component 404 can at least partly meet adrenal gland, and mitigate the anti-of adrenal gland treatment lead 400 Property.In some cases, paddle component 404 can be implanted between capsule and adrenal gland, this can further mitigate adrenal gland and control Treat the resistance of lead 400.In other cases, lead main body 406 and/or paddle component 404 can also include one or more Barb, one or more rigid helical parts and/or one or more pawl (not shown), for being mechanically attached to adrenal gland.Draw Line main body 406 can also include suture feature (for example, suture hole, suture can be arranged by the suture hole) with incite somebody to action Lead main body 406 is secured in place.In other cases, other than mechanical attachment mechanism or instead of mechanical attachment machine Tissue glue, adhesive and/or hydrogel or hydrogel/polymer type can be applied to lead main body 406 and/or paddle by structure Shape component 404 is to be attached to adrenal gland for lead main body 406 and/or 404 adhesive of paddle component.

Fig. 4 C is adrenal gland shown in Fig. 4 A- Fig. 4 B according to an embodiment of the present disclosure being deployed on adrenal gland 412 The example diagram for treating lead 400.As shown in Fig. 4 C, paddle component 404 is bent and is configured to engage and be attached on kidney A part of gland 412.The doctor for placing adrenal gland treatment lead 400 can with fluoroscopy observe the orientation of multiple electrodes 408. In other cases, one or two of lead main body 406 and paddle component 404 may include radiopaque marker (not shown), to help to make adrenal gland treatment lead 400 to visualize.In some cases, paddle component 404 can be wrappage Or mesh.

Fig. 4 D is that adrenal gland shown in Fig. 4 A- Fig. 4 C according to an embodiment of the present disclosure including tether 414,416 is controlled Treat the example diagram of lead 400.Tether 414,416 can be attached to paddle component 404, and facilitate 404 phase of paddle component Repositioning for adrenal gland 412.Tether 414,416 can extend from paddle component 404 and along lead main body 406.? In some cases, tether 414,416 can extend along the whole length of lead main body 406, and doctor or user are grasped Vertical tether 414,416.In other cases, tether 414,416 can be attached to the part of lead main body 406, so that lead master The manipulation of body 406 manipulates tether 414,416 and paddle component 404 indirectly.Tensing tether 414,416 can be in deployment system Paddle component 404 is recalled in 402.It allows disposing or removing completely from deployment system 402 as a result, tensing tether 414,416 Adrenal gland relocates paddle component 404 after treating lead 400.More specifically, paddle component 404 can be redeployed as Delivering configuration, as shown in Fig. 4 A, and if paddle component 404 as needed positioning or with deployment system 402 together It removes, then redeploys from adrenal gland 412.

Fig. 5 is the example diagram of adrenal gland treatment lead 500,502 according to an embodiment of the present disclosure.Adrenal gland is shown to control Lead 500,502 is treated to be arranged on the adrenal gland 504,506 of patient.Adrenal gland 504,506 is located on the kidney 508,510 of patient Side is located at the vena cave 512 of patient and the either side of aorta 514.Adrenal gland treatment lead 500,502 can pass through abdominal cavity Videoendoscopic surgery, open laparotomy ventrotomy or other Minimally Invasive Surgeries directly or indirectly deliver and be attached to adrenal gland 504,506 (or Gerota fascia).

Adrenal gland treatment each of lead 500,502 can have lead main body 516,518 and therewith arrange The set of multiple electrodes 520,522.Multiple electrodes collection uraphetine, 522 can be longitudinally arranged along adrenal gland 504,506.Certain In the case of, the distal portions of each lead main body 516,518 (for example, part with multiple electrodes collection uraphetine, 522) can be with With the bigger flexibility of the other parts than lead main body 516,518 (for example, more flexible polyurethane) or each lead main body 516,518 distal portions can by other materials (Polyethylene or(polyester)) it is formed.When being attached to When adrenal gland 504,506, the increased flexibility of the part of lead main body 516,518 or lead main body 516,518 can help to subtract The movement of light adrenal gland treatment lead 500,502.The increased flexibility of the part of lead main body 516,518 may be used as strain and subtract Light mechanism so that in the other parts of lead main body 516,518 assign (imparted) other parts in movement by every From and/or indirectly absorb.In other cases, lead main body 516,518 in each of adrenal gland treatment lead 500,502 can With between adrenal gland 504,506 and the implantation position for the controller for being couple to each lead main body 516,518, with additional length Degree or relaxation are attached to adrenal gland 504,506, so that the absorption of the movement for patient provides additional flexibility.

Each lead main body 516,518 can also include button 524,526.The button of each lead main body 516,518 524,526 can have than the bigger flexibility of each lead main body 516,518, and can be configured as meet adrenal gland 504, 506 to be attached thereon.More specifically, each button 524,526 can take the shape of adrenal gland 504,506.Adrenal gland 504,506 (as being further shown specifically in Fig. 6) is surrounded by adipose capsule.Each button 524,526 can be attached to the outer of capsule Surface, intracapsular, capsule inner surface (for example, between capsule and adrenal gland), or it is directly attached to adrenal gland 504,506.

In some cases, each lead main body 516,518 and/or each button 524,526 may include for machinery It is attached to the one or more barbs, one or more rigid helical parts and/or one or more pawls of adrenal gland 504,506 (not It shows).It in other cases, can be by tissue glue, adhesive other than mechanical attachment mechanism or instead of mechanical attachment mechanism And/or hydrogel is applied to each lead main body 516,518 and/or each button 524,526, be attached to adrenal gland 504, 506。

As mentioned above, adrenal gland treatment lead 500,502 can connect (for example, as shown and join with controller Examine Fig. 1 and Fig. 2 description).Controller can be configured as, and instruction passes through one or more in multiple electrodes collection uraphetine, 522 A electrode delivers stimulation energy, is released with adjusting from the catecholamine of the chromaffin cell at least one of adrenal gland 504,506 It puts.In some cases, controller can be configured as intermittently or continuously instruction and pass through in multiple electrodes collection uraphetine, 522 The various combinations of one or more electrodes deliver stimulation energy.More specifically, controller (not shown) may include circuit (for example, as described in Figure 1), instruction based on catecholamine metabolism the time or patient clinical sign and in work week Interim one or more electrodes by multiple electrodes collection uraphetine, 522 deliver stimulation energy.Duty cycle may include Apply stimulation in 25% period (for example, a few minutes, one hour or one day), and in 75% period (for example, rather Clock, one hour or one day) in inhibit (withhold) stimulation.Pass through the continued stimulus in one or more adrenal gland 504,506 It may be not necessarily required to reach the treatment level of catecholamine.Due to the adaptation or loss of adrenal gland 504,506, delivering stimulation energy The duty cycle control of amount can reduce battery consumption and reduce the chance of the validity to decay at any time.In addition, stimulation energy Amount can between 2Hz and 20kHz frequency (for example, 2Hz-50Hz, 50Hz-100Hz, 100Hz-500Hz, 500Hz-1kHz, 1kHz-5kHz, 5kHz-10kHz, 10kHz-20kHz or any combination thereof) delivering.Stimulation energy can be used as including with 2Hz and The energy burst of the pulse of frequency between 20kHz and apply or be applied continuously in.In addition, frequency and/or pulse width stimulation Energy can also continuously change or be periodically changed at any time.Due to the adaptation of adrenal gland 504,506, change electric current, Frequency and/or pulse width can reduce the chance of the validity of the decrease of stimulation at any time.In any of these cases, it responds In the patient feedback based on patient body symptom, thus it is possible to vary the stimulation energy delivered.

In addition, stimulation energy can be sent in a manner of monopole or multipole (for example, bipolar, three extremely etc.) adrenal gland 504, 506.When the one or more electrodes selected in multiple electrodes collection uraphetine, 522 are activated and stimulation energy is delivered to group When knitting, unipolar stimulation occurs.When two electrodes in multiple electrodes collection uraphetine, 522 are activated as anode and cathode, occur Bipolar stimulation (a type of multipole stimulation), so that sending stimulation energy between the electrode of activation.When multiple electrodes set 520, when more than two (for example, three, four etc.) electrode in 522 is activated, such as two as anodes and third Cathode is used as cathode or two and third is used as anode, and multipole stimulation can also occur.In addition, stimulation energy It can be subdivided across one or more electrodes in multiple electrodes 520, and across one or more electrodes in multiple electrodes 522 Dividually segmented.

In some cases, controller can indicate one be once delivered to stimulation energy in adrenal gland 504,506. In addition, controller can be tested between electrode sets 520,522, to determine which of electrode sets 520,522 are real Desired response (for example, level based on catecholamine in patient feedback and/or measurement patient) is showed.More specifically and In some cases, one in adrenal gland 504,506 for another in adrenal gland 504,506 compared to can differently respond Stimulation.Measurement result accordingly, in response to biosensor and/or the input from patient, controller can change stimulation Delivering is to target one or two of adrenal gland 504,506, to realize desired response.Stimulation energy can be delivered to electricity One or two of polar set 520,522, to coordinate the stimulation of adrenal gland 504,506.Two adrenal gland 504,506 can be same When be stimulated, or being applied to stimulation thereon can staggeredly (for example, according to duty cycle as mentioned above).In certain feelings Under condition, the coordination stimulation of adrenal gland 504,506 can reduce adaptation/tolerance due to adrenal gland 504,506 and cause at any time The chance of the validity of decrease.The sensing level of the catecholamine discharged can be used as feedback and be supplied to controller, controller Stimulation energy be can change to reach desired catecholamine emission levels.

Illustrative components shown in Fig. 5 are not intended to be proposed to appoint to the use scope or function of the embodiment of published subject What is limited.Illustrative components also should not be interpreted as having with there is shown with any single component or component combine related What dependence or requirement.In addition, in embodiment, any one or more components described in any one of Fig. 1-Fig. 4 It can be integrated with the various other components (and/or unshowned component) wherein described, all these components are considered as In the range of disclosed theme.For example, the system knot that adrenal gland stimulation lead 500,502 can be described with reference Fig. 1 and Fig. 2 It closes and uses.In addition, adrenal gland stimulation lead 500,502 may include showing in Screw Anchor 312 as shown in Figure 3 or such as Fig. 4 Thermoelectric element 410 or paddle component 404 out.

Fig. 6 is the example diagram of adrenal gland treatment system 600 according to an embodiment of the present disclosure.Adrenal gland treatment system 600 include: controller 602 (for example, impulse generator), accommodates electronic device and other assemblies；Adrenal gland stimulates lead 604, it is couple to controller 602；And optionally biosensor 606.It may include lead master that adrenal gland, which stimulates lead 604, Body 608 is configured to the adrenal gland 610 of engagement patient 620.More specifically, lead main body 608 is configurable to engagement adrenal gland 610 capsule 612.Fig. 6 further includes the insertion portion for highlighting the anatomical structure of adrenal gland 610.Capsule 612, which surrounds, is located at kidney 622 The adrenal gland 610 of top.Lead main body 608 can be attached to the outer surface of capsule 612, in capsule 612, the inner surface (example of capsule 612 Such as, between capsule and the remainder of adrenal gland 610).Adrenal gland 610 further includes the cortex 614 and marrow for generating steroid hormone Matter 616.Chromaffin cell synthesis, storage and catecholamine secretion (such as norepinephrine, dopamine) in medullary substance 616.Draw Line main body 608 could be attached to cortex 614 or medullary substance 616 (by as example with reference to the mechanical attachment machine described in Fig. 3 A- Fig. 3 C Structure or adhesive attachment mechanism).

Lead main body 608 further includes the multiple electrodes 618 arranged along lead main body 608.Multiple electrodes 618 can be matched It is set to and delivers stimulation energy by least one of multiple electrodes 618 to adjust the youngster from the chromaffin cell in adrenal gland 610 The release of tea phenol amine.It is physically connected to lead main body 608 and the controller 602 for being conductively coupled to multiple electrodes 618 is configurable to refer to Show and is discharged by one or more delivering stimulation energies in multiple electrodes 618 with adjusting from the catecholamine of chromaffin cell.Thorn Sharp energy can be sent to adrenal gland 610 in a manner of monopole or multipole (for example, bipolar, three extremely etc.).It is selected when in multiple electrodes 618 When one or more electrodes out are activated and send tissue for stimulation energy, unipolar stimulation occurs.When in multiple electrodes 618 Two electrodes when being activated as anode and cathode, occur bipolar stimulation (a type of multipole stimulation), so that in activation Stimulation energy is sent between electrode.When more than two (for example, three, four etc.) electrode in multiple electrodes set 618 is swashed When living, such as two as anode and third is used as cathode as cathode or two and third is used as anode, Multipole stimulation can occur.In addition, stimulation energy can be subdivided across one or more electrodes in multiple electrodes 618.Release The level of catecholamine controller 602 can be sensed and is provided as feedback to by biosensor 606, this can change Stimulation energy is to reach desired catecholamine emission levels.

In some cases, controller can be configured as intermittently or continuously instruction and pass through in multiple electrodes 618 One or more various combination delivers stimulation energy.In addition, controller 602 may include circuit (for example, as with reference to Fig. 1 Description), indicate the metabolism time based on catecholamine in the duty cycle by one or more of multiple electrodes 618 To deliver stimulation energy.Duty cycle may include applying within 25% period (for example, a few minutes, a few houres or several days) Stimulation, and inhibit stimulation within 75% period (for example, a few minutes, a few houres or several days).Deliver the work of stimulation energy The battery consumption of controller 602 can be reduced by making period control.Furthermore it is possible to deliver stimulation with the frequency between 2Hz and 20kHz Energy.Stimulation energy can be used as including being applied with the energy burst of the pulse of the frequency between 2Hz and 20kHz or continuously Apply.In addition, frequency and/or pulse width stimulation and/or current energy can also continuously change or at any time periodically Ground changes.

It can be in response to changing delivered stimulation energy based on the patient 620 of the physical symptom of patient 620 feedback.Separately Outside, the stimulation energy that controller 602 one or more of can indicate to be supplied to multiple electrodes 618 based on patient feedback Change.It can be set by the variation based on physical symptom or based on the data obtained by biosensor 606 and/or based on outside Standby upper patient 620 or doctor's input (communicatively coupled with the controller 602 that can control stimulation energy level) and be calibrated to The target level of catecholamine release is treated to customize.Patient 620 can activate/deactivate and his/her is to its symptom Perceptually relevant treatment (for example, when they feel the symptom of confirmed fatigue, they can be with activation therapeutic).In these feelings Under condition, controller 602 may include from restriction scheme to avoid catecholamine loss (for example, controller 602 a period of time Lower or close afterwards stimulation) so that patient will not lead to the loss of catecholamine and requiring continued treatment.

In some cases, biosensor 606 can be configured as at least one physiological reaction of measurement patient 620. Other than communicatedly (and physically) being couple to lead 604, controller 602 can also be communicatively coupled to biosensor 606.Controller 602 can be configured as at least one physiological reaction for receiving from biosensor 606 and having instruction patient 620 Data signal.Communication between controller 602 and biosensor 606 can be or including wireless communication link is all Such as such as short range radio links, bluetooth, IEEE 802.11 and/or proprietary wireless protocols etc. are (as referred to Fig. 2 into one Step detailed description).Controller 602 can also analyze the signal from biosensor 606 to calculate the change of stimulation energy, And it is communicated based on the analysis to signal with lead 604 to change stimulation energy.

In some cases, biosensor 606 can be arranged to receive the separated sensor of physiological signal.At other In the case of, biosensor 606 can be controller 602 itself.In addition, biosensor 606 can be it is long-range implantable or Wearable monitoring system (being communicated with controller 602).Biosensor 606 can also be connected to it is independent in controller 602 Sense lead.Independent sense lead can monitor the signal of another target from the adrenal gland 610 far from patient 620, with Capture one or more physiological signals (for example, instruction blood pressure).Adrenal gland treatment system 600 may include one in these aspects It is a or multiple as biosensor 606.

In some cases, biosensor 606 can be configured as measurement at least one of the following: patient's 620 Heart rate, the heart rate variability (such as modulation of S1/S2 amplitude and breathing) of patient 620, the respiratory rate of patient 620, patient 620 Activity level, the catecholamine levels (for example, chemical sensor) of patient 620, metanephrine level, metanephrine, flesh Acid anhydrides (urine) ratio levels, metanephrine as the substitute of plasma norepinephrine, patient 620 body posture, The body temperature of patient 620, the temperature of adrenal gland 610, the cardiac output of patient 620 and the angiosthenia of patient 620, or any combination thereof (for example, heart rate/respiratory rate ratio).The activity level of patient 620 can assist notification controller 602: due to what is recycled and recycle The amplitude of variation noticed in catecholamine, if (for example, increase or prevent) stimulation energy should be changed.In certain situations Under, biosensor 606 can be implanted into bladder and determine that the urine metanephrine of patient 620 is horizontal, be first kidney The substitute of upper parathyrine level.The variation of physiological reaction above-mentioned may need to adjust exocytosis or the generation of catecholamine It thanks, so as to cause the change of required physiological reaction.As a result, controller 602 can change and (increase or decrease) stimulation energy with Change and adjust release of the catecholamine from adrenal gland 610, to maintain the aspiration level of the catecholamine in patient 620.

In some cases, biosensor 606 can be configured as the body temperature of measurement patient 620.Biosensor 606 The stroke output of measurement cardiac output, heart be can be additionally configured to (for example, S1 instruction shrinkage or S2 are indicated by sympathetic mind Through blood pressure caused by activity), mean arterial pressure/pulse pressure/contraction of the shrinkage main body of heart, and/or patient 620/relax It opens (via intra-arterial or artery Zhou Fangfa).Biosensor 606 can also measure other substitutes of catecholamine levels, or The pain of various morbid states with neurohormone or neurotransmitter dysfunction or non-pain symptom, such as fibromyalgia (for example, as indicated by fatigue), confirmed fatigue or sleep apnea etc..In some cases, biosensor 606 can be with Be configured to measurement to orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), that orthostatic does not tolerate (OI) is related The substitute of the substitute of the catecholamine levels of connection or catecholamine levels associated with heart failure and migraine, institute There are these variations all with circulating catecholamines level to have causality.Biosensor 606 can also measure the expiration of reduction Positive pressure (PEP), the original left ventricular ejection time (LVET) reduced and/or the increased LVET for heart rate correction.Above-mentioned life The variation of reason reaction may need the adjusting of metabolism and the exocytosis of catecholamine.As a result, the adjustable stimulation energy of controller 602 Amount is to adjust the release of catecholamine from adrenal gland 610, to maintain the aspiration level of catecholamine in patient 620.

The coordination stimulation provided by controller 602 can provide closed-loop system, use systemic catecholamine or disease The marker of state is treated to optimize.In some cases, two or more physiological parameters are that controller 602 provides closed loop control It makes and enabled predictive ability (such as is stimulated with only providing treatment when needed or otherwise enabling improved treatment and titrate Amplitude, charge) and optimize clinical effectiveness.In order to which the stable state defect for solving adrenal gland 610 (or body of gland) or instantaneous defect are (on quickly The ability of liter/decline), more than one biosensor 606 can be used in system 600, as described above and controller 602 communications.Sensor can provide additional quantization, measurement result and track depending on movable catecholamine levels or disease State is to optimize treatment.The measurement result of various biosensors can be collected and be assembled by controller 602 to change by more The delivering for the stimulation energy that a electrode 618 provides.

Biosensor 606 can be by determining the life measured under given stable state activity level by biosensor 606 Reason reacts to measure the stable state defect of the catecholamine levels of patient 620." the wink of activity state transition can be surrounded by observing State " biosensor 606 measurement result monitors instantaneous defect.In some cases, it is directed to the catechol for maintaining patient 620 Amine level, desired response will be quick and be more like " underdamping (underdamped) " system, can will see without benign Come as overdamping system.In some cases, controller 602 can be programmed based on patient's customization.For example, patient can It can prefer stimulation energy associated with lower systematicness catecholamine.Therefore, which can be programmed for by controller 602 Iteration in this way.Another patient may prefer to the state with higher systemic catecholamine, this will lead to difference Stimulation energy (for example, with the patient of lower systemic catecholamine is liked in comparison).Controller 602 can use patient Intracorporal reference programming changes stimulation energy based on the time (awake/sleep) in activity level and one day.It is raw Substance markers object data can be used for calibrating on the basis of patient one by one in the systemic catecholamine levels in closed-loop system Patient's preference (increases or decreases).

As a specific example, biosensor 606 can be configured as monitoring heart rate activity.In patient 620, physiology is passed Sensor 606 can continuous recorded heart rate (HR) and activity (movement) information (for example, using accelerator) or body gesture (for example, It is upright uneven), and be discrete active belt by parsing of the data stream.For the transformation between active belt, time shaft is separation 's.HR data around transformation can produce the measurement of transient state defect, and from intermediate change and be sufficiently far from the HR of transformation Data can produce the data of stable state defect.In some cases, instead of monitor patient 620 heart rate or with monitoring patient 620 Heart rate together, biosensor 606 can measure heart sound.It is awake or sleeping that heart sound, which can be provided about patient 620, Instruction with influence catecholamine levels adjusting.More specifically, when patient 620 during sleep, when patient awoke compared with and Speech, controller 602 can be programmed to optimization (reduction) catecholamine levels to pass through what multiple electrodes 618 provided by reducing Irritation level avoids having a sleepless night.It can be with maintaining stimulus parameter to ensure that catecholamine levels are maintained on lower limit (low circulation Catecholamine levels may be associated with the challenge that patient can not fall asleep at present) or lower than the upper limit.In addition, working as patient 620 When exercise, controller 602 may insure optimum level to mitigate pain and fatigue (for example, changing labour or pressure based on baseline To adjust level) and ensure catecholamine levels to be maintained at lower limit or more that (higher cyclical level can be current with these patients Challenge lower to the tolerance of long term activity of earthquake is associated).As a result, controller 602 can be configured to ensure that catecholamine levels Appropriate adjusting, can patient exercise, rest or experience pressure experience time-varying.

Illustrative components shown in Fig. 6 are not intended to be proposed to appoint to the use scope or function of the embodiment of published subject What is limited.Illustrative components also should not be interpreted as having with there is shown with any single component or component combine related What dependence or requirement.In addition, in embodiment, any one or more components described in any one of Fig. 1-Fig. 5 It can be integrated with the various other components (and/or unshowned component) wherein described, all these components are considered as In the range of published subject.For example, adrenal gland stimulation lead 602 can make in conjunction with the system that reference Fig. 1 and Fig. 2 are described With.In addition, adrenal gland stimulation lead 604 may include Screw Anchor 312 as shown in Figure 3 or thermoelectricity as shown in Figure 4 Element 410 or paddle component 404.

Fig. 7 A is the example diagram of another adrenal gland treatment system according to an embodiment of the present disclosure.Fig. 7 shows patient Anatomical structure 700 various aspects, including aorta 702, vena cave 704, right kidney 706, left kidney 708,710 and of right adrenal gland Left adrenal gland 712.The some aspects of vascular system also highlight, comprising: artery 714 on upper right kidney, artery on kidney in the right side 716, artery 718 on the kidney of bottom right, artery 720 on the kidney of upper left, artery 722 on left kidney, on the kidney of lower-left under artery 724, left and right diaphragm Artery 726.Adrenal gland treatment system may include that thermoelectric element (shown in Fig. 7 B) is attached or coupled to the one of vascular system A or multiple position 728a-h.Thermoelectric element can cool down one or two of adrenal gland 710,712, to adjust catecholamine It is discharged from chromaffin cell therein.

Fig. 7 B is according to an embodiment of the present disclosure include the adrenal gland treatment system shown in Fig. 7 A cooling system 730 example diagram.Cooling system 730 can be attached to one or more position 728a-h shown in Fig. 7 A.In position At 728a-h, the cooling blood flow for flowing into adrenal gland 710,712 of cooling system 730.Cooling blood can cool down adrenal gland 710,712 Neighboring area, this can trigger from the catecholamine of the chromaffin cell in adrenal gland 710,712 discharge.As a result, cooling system 730 can have the effect for increasing the cyclical level of norepinephrine and dopamine in blood flow, be similarly to adrenal gland 710,712 stimulation.Cooling system 730 can be used alone or with herein (for example, Fig. 1-Fig. 6) discuss stimulating system or Lead is applied in combination.More specifically, cooling system 730 may include controller 732.Controller 732 can apply electric current to apply Add cooling effect.Controller 732 can also be couple to adrenal gland stimulation lead, as (for example, Fig. 1-Fig. 6) is discussed herein, To control the stimulation for being applied to adrenal gland 710,712.Controller 732 can apply cooling and stimulation simultaneously, or be alternately cooled And stimulation.This can increase the battery life of controller 732 by reducing battery consumption, and can also reduce due on kidney The adaptation or loss of gland 710,712 and cause the chance of validity to decay at any time.

Cooling system 730 may include at least one thermoelectric element (for example, peltier-element) with realize to adrenal gland 710, 712 cooling.As shown in Fig. 7 B, bracket or wrappage 744 is disposed in artery 742 or the position of the vascular system of surrounding Set the place one of 728a-h.In some cases, bracket or wrappage 744 can be directly arranged at one in adrenal gland 710,712 It is a or two on.Bracket or wrappage 744 include the thermoelectric element that controller 730 is couple to via insulated conductor 738,740.Control Device 732 processed can apply electric current 734,736 via insulated conductor 738,740, and distribute the heat generated by thermoelectric element.It is cold But system 730 can provide cooling within the temperature range of 4 degrees Celsius to 32 degrees Celsius.

Illustrative components shown in Fig. 7 A- Fig. 7 B are not intended to use scope or function to the embodiment of published subject It is proposed any restrictions.Illustrative components also should not be interpreted as having with there is shown with any single component or component combined Any dependence or requirement closed.In addition, in embodiment, describe in any one of Fig. 7 A- Fig. 7 B any one or Multiple components can be integrated with various other components (and/or unshowned component) for wherein describing, all these components all by It is considered within the scope of the disclosed subject matter.For example, system or reference that cooling system 730 can be described with reference Fig. 1 and Fig. 2 The adrenal gland stimulation lead and system of Fig. 3-Fig. 6 description are used in combination.

Without departing from the scope of the disclosure, the exemplary embodiment discussed can be carry out various modifications and Addition.Although the scope of the present disclosure further includes that there is different characteristic to combine for example, above-described embodiment is related to special characteristic Embodiment and do not include be described feature embodiment.Therefore, the scope of the present disclosure, which is intended to include, falls into claim model Enclose interior all these substitutions, modifications and variations and its all equivalent.

Claims

1. a kind of device for the delivering treatment of the adrenal gland of patient, described device include:

Lead main body is configured to attach to adrenal a part of the patient and engages the adrenal capsule； And

Multiple electrodes arrange that at least one of the multiple electrode is configured as delivering stimulation along the lead main body Energy is discharged with adjusting from the catecholamine of the chromaffin cell in the adrenal gland.

2. the apparatus according to claim 1, wherein the lead main body be configured to attach to the adrenal capsule or Capsule week connective tissue.

3. device according to any one of claim 1 or 2, wherein the lead main body is configured to attach in following At least one: capsule week connective tissue, the outer surface of the adrenal capsule, the adrenal capsule inner surface, Yi Jisuo Between the inner surface and the outer surface for stating adrenal capsule.

4. device according to any one of claim 1-3 passes through the lead wherein the lead main body is configured as At least one in mechanical attachment and the adhesive attachment of adrenal a part or capsule week connective tissue of main body and the patient It is a, and it is attached to adrenal described a part of the patient.

5. device according to claim 4, wherein the lead main body further includes in barb, sutural lamina, helical member and pawl At least one, with adrenal a part for the lead main body to be mechanically attached to the patient.

6. device according to claim 4 further includes at least one of tissue glue, adhesive and hydrogel, to be used for The lead main body is attached to adrenal a part of the patient.

7. device according to claim 1 to 6, wherein at least one of the multiple electrode includes piercing through Partially and it is configured as being pierced into the adrenal gland.

8. device according to claim 7, wherein be configured as described in the multiple electrodes being pierced into the adrenal gland At least one is additionally configured to deliver the stimulation energy is released with adjusting from the catecholamine of the chromaffin cell in the adrenal gland It puts.

9. device according to claim 1 to 8 further includes biosensor, the biosensor is configured For measure at least one of the following: the heart rate of the patient, the heart rate variability of the patient, the patient respiratory rate, The activity level of the patient, the catecholamine levels of the patient, the catecholamine metabolism object of the patient, the patient Metanephrine level, the creatinine levels in the Urine in Patients, the trouble of horizontal, the described patient of normetanephrine The posture of horizontal, the described patient of the cortisol metanephrine of person, the body temperature of the patient, the cardiac output of the patient, institute State the Depth of sleep of the angiosthenia of patient, the sleep state of the patient and the patient.

10. device according to claim 9, wherein measurement result in response to the biosensor and coming from the trouble At least one of input of person changes the stimulation energy.

11. device according to claim 9 further includes controller, the controller is configured as sensing with the physiology Device communication and the delivering that the stimulation energy is indicated in response to the communication.

12. device described in any one of -11 according to claim 1 further includes controller, the controller is configured to, instruction The stimulation energy is delivered by least one electrode in the multiple electrode, it is thin from the thermophilic chromium in the adrenal gland to adjust The catecholamine of born of the same parents discharges.

13. device according to claim 12, wherein the controller is configured as, and intermittently or continuously instruction is logical The Different electrodes set for crossing the multiple electrode delivers the stimulation energy.

14. device according to claim 12, wherein the controller is configured as, and indicates the generation based on catecholamine Thank to the time on the duty cycle by least one electrode delivering stimulation energy in the multiple electrode.

15. device according to claim 12, wherein the controller is configured as, and is indicated between 2Hz and 20kHz Frequency the stimulation energy is delivered by least one electrode in the multiple electrode.